Phenotype of Cluster Headache: Clinical Variability, Persisting Pain Between Attacks, and Comorbidities—An Observational Cohort Study in 825 Patients

Abstract

Introduction: Cluster headaches can occur with considerable clinical variability. The interand intra-individual variability could contribute to the fact that the clinical headache phenotype is not captured by too strict diagnostic criteria, and that the diagnosis and the effective therapy are thereby delayed. The aim of the study was to analyze the severity and extent of the clinical symptoms of episodic and chronic cluster headaches with regard to their variability and to compare them with the requirements of the International Classification of Headache Disorders 3rd edition (ICHD-3) diagnostic criteria. Methods: The study was carried out as a crosssectional analysis of 825 patients who had been diagnosed with cluster headaches by their physician. Using an online questionnaire, standardized questions on sociodemographic variables, clinical features of the cluster headache according to ICHD-3, and accompanying clinical symptoms were recorded. Results:The majority of patients with cluster headaches have clinical features that are mapped by the diagnostic criteria of ICHD-3. However, due to the variability of the symptoms, there is a significant proportion of clinical phenotypes that are not captured by the ICHD-3 criteria for cluster headaches. In addition, change in the side of the pain between the cluster episodes, pain location, as well as persisting pain between the attacks is not addressed in the ICHD-3 criteria. In the foreground of the comorbidities are psychological consequences in the form of depression, sleep disorders, and anxiety. Conclusions: The variability of the phenotype of cluster headaches can preclude some patients from receiving an appropriate diagnosis and effective therapy if the diagnostic criteria applied are too strict. The occurrence of persisting pain between attacks should also be diagnostically evaluated due to its high prevalence and severity as well as psychological strain. When treating patients with cluster headaches, accompanying psychological illnesses should carefully be taken into account.

Association of Clinical and Neuroanatomic Factors With Response to Ventral Tegmental Area DBS in Chronic Cluster Headache

“…There is a slight preponderance for right-sided attacks in cluster headache. 25 Taken together with better responses in those with right-sided attacks, it suggests that the pain neuromatrix may have some form of lateralization which both makes patients more prone to right-sided attacks and more likely to respond to treatment if attacks are right-sided. We hypothesized that patients with comorbid affective disorders or other chronic pain conditions may be less likely to respond because these has been shown to be negative predictive factors of response to occipital nerve stimulation for chronic headache disorders, but this was not borne out by the results.…”

Cluster Headache Pathophysiology—A Disorder of Network Excitability?

“…Persistent pain between attacks and allodynia, which are prevalent among CH patients, refs. [40][41][42] indicate increased sensitivity. The chronology of central sensitization in CH is unstudied; in particular, we do not know whether sensitization precedes the bout or is a consequence thereof.…”

Patient-identified burden and unmet needs in patients with cluster headache: An evidence-based qualitative literature review

“…This results in a limited understanding of the triggers and temporal course of the condition. 3,5 Variability in the clinical presentation, 6 misdiagnosis of symptoms as being migraine-related, 7 and the lack of understanding and awareness, 8 particularly among primary care physicians, contribute to diagnostic delays of several years for most patients with cluster headache. 7,9 A recent study identified that up to 50% of patients were diagnosed with cluster headache by a neurologist, indicating that misdiagnosis or inappropriate treatment may have come from other specialists or self-diagnosis.…”